Terrestrial carbon fluxes are sensitive to climate change, but the interannual climate sensitivity of the land carbon cycle can also change with time. We analyzed the changes in responses of net biome production (NBP), net primary production (NPP), and heterotrophic respiration (Rh) to interannual climate variations over the 21st century in the Earth System Models (ESMs) from the Coupled Model Intercomparison Project 5. Under Representative Concentration Pathway (RCP) 4.5, interannual temperature sensitivities of NBP ((Temp)(NBP)), NPP ((Temp)(NPP)), and Rh ((Temp)(Rh)) remain relatively stable at global scale, yet with large differences among ESMs and spatial heterogeneity. Modeled (Temp)(NPP) and (Temp)(Rh) appear to increase in parallel in boreal regions, resulting in unchanged (Temp)(NBP). Tropical (Temp)(NBP) decreases in most models, due to decreasing (Temp)(NPP) and relatively stable (Temp)(Rh). Across models, the changes in (Temp)(NBP) can be mainly explained by changes in (Temp)(NPP) rather than changes in (Temp)(Rh), at both global and regional scales. Interannual precipitation sensitivities of global NBP ((Prec)(NBP)), NPP ((Prec)(NPP)), and Rh ((Prec)(Rh)) are predicted not to change significantly, with large differences among ESMs. Across models, the changes in (Prec)(NBP) can be mainly explained by changes in (Prec)(NPP) rather than changes in (Prec)(Rh) in temperate regions, but not in other regions. Changes in the interannual climate sensitivities of carbon fluxes are consistent across RCPs 4.5, 6.0, and 8.5 but larger in more intensive scenarios. More effort should be considered to improve terrestrial carbon flux responses to interannual climate variability, e.g., incorporating biogeochemical processes of nutrient limitation, permafrost dynamics, and microbial decomposition.